Diabetic retinopathy, the retinal vascular disease secondary to diabetes, is the leading cause of new cases of blindness among persons aged 20 to 74 years. Treatment of diabetic retinopathy has been aimed at retarding its progress and limiting the severe stages of proliferative retinopathy. However, the development of ophthalmoscopic changes of diabetic retinopathy, as evidenced by fluorescein angiography, may be a relatively late manifestation of vascular complications in the retina. Because of the potentially devastating effects of retinopathy on vision, it is highly desirable to identify non-invasive precursors to the breakdown of the blood-retinal barrier. Unfortunately, standard clinical measures of vision (e.g. visual acuity) are quite insensitive in detecting subtle changes even after the onset of retinopathy. Our laboratory studies have demonstrated that many diabetics, even prior to the development of retinopathy, show large and specific losses of vision function; these losses appear to be restricted to the chromatic pathways and involve a reduction of sensitivity in the blue-sensitive B cone receptor mechanism. A central aim of this work is to identify the retinal site of this sensitivity loss. The specific aims in the studies outlined in this proposal are consistent with the more general long term objective of reducing the retinal vascular consequences of diabetes that lead to severely reduced vision and blindness. The studies are intended to provide non-invasive vision measures which can be used prior to a breakdown in the blood-retinal barrier, to monitor the efficacy of medical and surgical treatments (including prophylactic treatment), and provide diagnostic and prognostic indicators for the treatment of diabetes and retinal complications of diabetes. The proposed research is intended to identify the receptoral and post-receptoral components of the B cone sensitivity loss. Psychophysical measures such as the Westheimer function, transient tritanopia, chromatic discrimination along cardinal directions, probe-flash techniques, and steady state lateral cone-cone interaction methodology will be utilized to probe post-receptoral and retinal sensitivity control mechanisms of the diabetic eye.